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Anti-proliferative, apoptosis inducing, and antioxidant potential of Callistemon lanceolatus bark extracts: an in vitro and in silico study

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Abstract

The present study reports anticancer and antioxidant activities of Callistemon lanceolatus bark extracts. Anticancer activity was studied against MDA-MB-231 cells. Antioxidant assessment of the chloroform and methanol extracts showed considerable free radical scavenging, metal ion chelating, and reducing power potential. Chloroform extract exhibited potent inhibition of cancer cell proliferation in MTT assay (IC50 9.6 μg/ml) and promoted programmed cell death. Reactive oxygen species (ROS) generation, mitochondria membrane potential (MMP) disruption ability, and nuclear morphology changes were studied using H2-DCFDA, JC-1, and Hoechst dyes, respectively, using confocal microscopy. Apoptotic cells exhibited fragmented nuclei, increased ROS generation, and altered MMP in dose- and time-dependent manner. Chloroform extract upregulated the BAX-1 and CASP3 mRNA expression coupled with downregulation of BCL-2 gene. Further, in silico docking of phytochemicals present in C. lanceolatus with anti-apoptotic Bcl-2 protein endorsed apoptosis by its inhibition and thus corroborated the experimental findings. Obatoclax, a known inhibitor of Bcl-2 was used as a reference compounds.

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Data availability

The data generated during the current study are available from the corresponding author on reasonable request.

References

  1. Singh AK, Singh SV, Kumar R, Kumar S, Senapati S, Pandey AK. Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise. World J Hepatol. 2023;15(1):1–18. https://doi.org/10.4254/wjh.v15.i1.1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Huang M, Lu JJ, Ding J. Natural products in cancer therapy: Past, present and future. Nat Prod Bioprospec. 2021;11:5–13. https://doi.org/10.1007/s13659-020-00293-7.

    Article  Google Scholar 

  3. Ganguly R, Kumar R, Pandey AK. Baicalin provides protection against fluoxetine-induced hepatotoxicity by modulation of oxidative stress and inflammation. World J Hepatol. 2022;14:729–43. https://doi.org/10.4254/wjh.v14.i4.729.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Singh AK, Singla RK, Pandey AK. Chlorogenic acid: A dietary phenolic acid with promising pharmacotherapeutic potential. Curr Med Chem. 2022. https://doi.org/10.2174/0929867329666220816154634.

    Article  PubMed  Google Scholar 

  5. Islam MdS, Rahi MdS, Jahangir CA, Rahman MH, Jerin I, Amin R, et al. In vivo anticancer activity of Basella alba leaf and seed extracts against Ehrlich’s ascites carcinoma (EAC) cell line. Evid-Based Complement Altern Med. 2018;2018:1–11. https://doi.org/10.1155/2018/1537896.

    Article  Google Scholar 

  6. Kushwaha PP, Kumar R, Neog PR, et al. Characterization of phytochemicals and validation of antioxidant and anticancer activity in some Indian polyherbal ayurvedic products. Vegetos. 2021;34:286–99. https://doi.org/10.1007/s42535-021-00205-1.

    Article  Google Scholar 

  7. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30. https://doi.org/10.3322/caac.21590.

    Article  PubMed  Google Scholar 

  8. Shin VY, Chen J, Cheuk IWY, Siu M-T, Ho C-W, Wang X, et al. Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness. Cell Death Dis. 2019;10:270. https://doi.org/10.1038/s41419-019-1513-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gupta A, Singh AK, Kumar R, Jamieson S, Pandey AK, Bishayee A. Neuroprotective potential of ellagic acid: a critical review. Adv Nutr. 2021;12:1211–38. https://doi.org/10.1093/advances/nmab007.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mitra S, Dash R. Natural products for the management and prevention of breast cancer. Evid-Based Complement Altern Med. 2018;2018:1–23. https://doi.org/10.1155/2018/8324696.

    Article  Google Scholar 

  11. Gupta A, Shridhar K, Dhillon PK. A review of breast cancer awareness among women in India: Cancer literate or awareness deficit. Eur J Cancer. 2015;51:2058–66. https://doi.org/10.1016/j.ejca.2015.07.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rakha EA, Reis-Filho JS, Ellis IO. Basal-like breast cancer: a critical review. J Clin Oncol. 2008;26:2568–81. https://doi.org/10.1200/JCO.2007.13.1748.

    Article  PubMed  Google Scholar 

  13. Kumar S, Pandey AK. Potential molecular targeted therapy for unresectable hepatocellular carcinoma. Curr Oncol. 2023;30:1363–80. https://doi.org/10.3390/curroncol30020105.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Pandey A, Kumar R, Mishra A, Pandey A, Pandey AK. Recent updates on the pharmacological potential of plant-based Rutin. Curr Nutraceut. 2022;3(2):e140622205967. https://doi.org/10.2174/2665978603666220614151613.

    Article  CAS  Google Scholar 

  15. Prescott C, Bottle SE. Biological relevance of free radicals and nitroxides. Cell Biochem Biophys. 2017;75:227–40. https://doi.org/10.1007/s12013-016-0759-0.

    Article  CAS  PubMed  Google Scholar 

  16. Gupta A, Singh AK, Loka M, Pandey AK, Bishayee A. Ferulic acid-mediated modulation of apoptotic signaling pathways in cancer. Adv Protein Chem Struct Biol. 2021;125:215–57. https://doi.org/10.1016/bs.apcsb.2020.12.005.

    Article  CAS  PubMed  Google Scholar 

  17. Kumar R, Singh AK, Gupta A, Bishayee A, Pandey AK. Therapeutic potential of Aloe vera—A miracle gift of nature. Phytomed. 2019;60:152996. https://doi.org/10.1016/j.phymed.2019.152996.

    Article  CAS  Google Scholar 

  18. Albensi BC. What is nuclear factor kappa B (NF-κB) doing in and to the mitochondrion. Front Cell Dev Biol. 2019;7:154. https://doi.org/10.3389/fcell.2019.00154.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lang F, Stournaras C. Ion channels in cancer: Future perspectives and clinical potential. Phil Trans R Soc B. 2014;369:20130108. https://doi.org/10.1098/rstb.2013.0108.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Yang M, Brackenbury WJ. Membrane potential and cancer progression. Front Physiol. 2013. https://doi.org/10.3389/fphys.2013.00185.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Pinton P, Giorgi C, Siviero R, Zecchini E, Rizzuto R. Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene. 2008;27:6407–18. https://doi.org/10.1038/onc.2008.308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Naoi M, Wu Y, Shamoto-Nagai M, Maruyama W. Mitochondria in neuroprotection by phytochemicals: Bioactive polyphenols modulate mitochondrial apoptosis system, function and structure. Int J Mol Sci. 2019;20:2451. https://doi.org/10.3390/ijms20102451.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ahmad K, Hafeez ZB, Bhat AR, Rizvi MA, Thakur SC, Azam A, et al. Antioxidant and apoptotic effects of Callistemon lanceolatus leaves and their compounds against human cancer cells. Biomed Pharmacother. 2018;106:1195–209. https://doi.org/10.1016/j.biopha.2018.07.016.

    Article  CAS  PubMed  Google Scholar 

  24. Kumar R, Gupta A, Singh AK, Bishayee A, Pandey AK. The Antioxidant and antihyperglycemic activities of bottlebrush plant (Callistemon lanceolatus) stem extracts. Medicines. 2020;7:11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Salem MZM, El-Hefny M, Nasser RA, Ali HM, El-Shanhorey NA, Elansary HO. Medicinal and biological values of Callistemon viminalis extracts: History, current situation and prospects. Asian Pacific J Trop Med. 2017;10:229–37.

    Article  CAS  Google Scholar 

  26. Mishra AK, Mishra A, Kehri H, Sharma B, Pandey AK. Inhibitory activity of Indian spice plant Cinnamomum zeylanicum extracts against Alternaria solani and Curvularia lunata, the pathogenic dematiaceous moulds. Ann Clin Microbiol Antimicrob. 2009;8:9. https://doi.org/10.1186/1476-0711-8-9.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Chang CC, Yang MH, Wen HM, Chern JC. Estimation of total flavonoid content in propolis by two complementary colometric methods. J Food Drug Anal. 2020. https://doi.org/10.38212/2224-6614.2748.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Singh RP, Chidambara Murthy KN, Jayaprakasha GK. Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in vitro models. J Agric Food Chem. 2002;50:81–6. https://doi.org/10.1021/jf010865b.

    Article  CAS  PubMed  Google Scholar 

  29. Oyaizu M. Studies on products of browning reaction: antioxidative activities of products of browning reaction prepared from glucosamine. Jpn J Nutr Diet. 1986;44:307–15. https://doi.org/10.5264/eiyogakuzashi.44.307.

    Article  CAS  Google Scholar 

  30. Dinis TCP, Madeira VMC, Almeida LM. Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Arch Biochem Biophys. 1994;315:161–9. https://doi.org/10.1006/abbi.1994.1485.

    Article  CAS  PubMed  Google Scholar 

  31. Negi PS, Jayaprakasha GK. Control of foodborne pathogenic and spoilage bacteria by garcinol and Garcinia indica extracts, and their antioxidant activity. J Food Sci. 2006;69:FMS61–5.

    Article  Google Scholar 

  32. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Meth. 1983;65:55–63. https://doi.org/10.1016/0022-1759(83)90303-4.

    Article  CAS  Google Scholar 

  33. Mechoulam H, Pierce EA. Expression and activation of STAT3 in ischemia-induced retinopathy. Invest Ophthalmol Vis Sci. 2005;46:4409. https://doi.org/10.1167/iovs.05-0632.

    Article  PubMed  Google Scholar 

  34. He X, Sun J, Huang X. Expression of caspase-3, Bax and Bcl-2 in hippocampus of rats with diabetes and subarachnoid hemorrhage. Exp Ther Med. 2017. https://doi.org/10.3892/etm.2017.5438.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Scoumanne A, Cho SJ, Zhang J, Chen X. The cyclin-dependent kinase inhibitor p21 is regulated by RNA-binding protein PCBP4 via mRNA stability. Nucleic Acids Res. 2011;39:213–24. https://doi.org/10.1093/nar/gkq778.

    Article  CAS  PubMed  Google Scholar 

  36. Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19:202–8.

    Article  CAS  PubMed  Google Scholar 

  37. Rana N, Singh AK, Shuaib M, Gupta S, Habiballah MM, Alkhanani MF, et al. Drug Resistance mechanism of M46I-mutation-induced Saquinavir resistance in HIV-1 protease using molecular dynamics simulation and binding energy calculation. Viruses. 2022;14:697. https://doi.org/10.3390/v14040697.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7:42717. https://doi.org/10.1038/srep42717.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kushwaha PP, Singh AK, Prajapati KS, Shuaib M, Gupta S, Kumar S. Phytochemicals present in Indian ginseng possess potential to inhibit SARS-CoV-2 virulence: A molecular docking and MD simulation study. Microb Pathog. 2021;157:104954. https://doi.org/10.1016/j.micpath.2021.104954.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dizdaroglu M, Jaruga P, Birincioglu M, Rodriguez H. Free radical-induced damage to DNA: Mechanisms and measurement. Free Rad Biol Med. 2002;32:1102–15. https://doi.org/10.1016/s0891-5849(02)00826-2.

    Article  CAS  PubMed  Google Scholar 

  41. Kushwaha PP, Singh AK, Shuaib M, Prajapati KS, Vardhan PS, Gupta S, et al. 3-O-(E)-p-Coumaroylbetulinic acid possess anticancer activity and inhibit Notch signaling pathway in breast cancer cells and mammosphere. Chem-Biol Int. 2020;328:109200. https://doi.org/10.1016/j.cbi.2020.109200.

    Article  CAS  Google Scholar 

  42. Uchiyama T, Tabata K, Nomura S, Kaneko Y, Fujimoto Y, Suzuki T. Induction of apoptosis in human leukemia cell (Jurkat) by neolignans isolated from seeds of licariapuchury-major. Biol Pharmaceut Bull. 2009;32:1749–53. https://doi.org/10.1248/bpb.32.1749.

    Article  CAS  Google Scholar 

  43. Rahman MDA, Hannan MDA, Dash R, Rahman MDH, Islam R, Uddin MJ, et al. Phytochemicals as a complement to cancer chemotherapy: Pharmacological modulation of the autophagy-apoptosis pathway. Front Pharmacol. 2021;12:639628. https://doi.org/10.3389/fphar.2021.639628.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rezaei PF, Fouladdel S, Hassani S, Yousefbeyk F, Ghaffari SM, Amin G, et al. Induction of apoptosis and cell cycle arrest by pericarp polyphenol-rich extract of Baneh in human colon carcinoma HT29 cells. Food Chem Toxicol. 2012;50:1054–9. https://doi.org/10.1016/j.fct.2011.11.012.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

RK acknowledges financial support from Council of Scientific and Industrial Research (CSIR), New Delhi in the form of Senior Research Fellowship and Indian Council of Medical Research (ICMR), New Delhi for Research Associate fellowship (File No. 3/2/3/65/2022/NCD-III). In vitro studies described in the current article are part of a PhD thesis of RK. PPK and AKS acknowledge ICMR and CSIR for financial support in the form of Senior Research Fellowships, respectively. RK and AKP also acknowledge UGC-SAP and DST-FIST facilities of Biochemistry Department, University of Allahabad, Prayagraj, India.

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AKP and SK conceptualized the idea. RK performed antioxidant experiments. RK, PPK, and AKS performed anticancer and in silico experiments. RK, SK, and AKP analyzed the data. RK wrote the first draft of the manuscript. AKP and SK critically reviewed and revised the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Abhay Kumar Pandey.

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Kumar, R., Kushwaha, P., Singh, A.K. et al. Anti-proliferative, apoptosis inducing, and antioxidant potential of Callistemon lanceolatus bark extracts: an in vitro and in silico study. Med Oncol 40, 169 (2023). https://doi.org/10.1007/s12032-023-02035-4

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