Caspase Activators: Phytochemicals with Apoptotic Properties Targeting Cancer, A Health Care Strategy to Combat this Disease

Abstract

Context: Caspases, a family of cysteine-aspartic proteases have a pivotal role in apoptotic pathways. Their down-regulation is reported to induce inappropriate cell survival and enhanced carcinogenic potential. Screening of phytochemicals with a capacity to activate caspases enhancing apoptotic capacity has been proven to be effective anticancer agents. Objectives: This review consolidates data on phtochemicals traditionally used to treat cancerous conditions. The scientific validation of caspaseactivated apoptosis for this traditional application has been compiled. Methods: Internet assisted scientific literature was collected from Google, Google Scholar, ResearchGate and NCI, restricted to publications from 1997 to 2019. Search terms 'caspases and cancer', 'assay of caspases', 'traditionally used medicinal plants', 'Kani tribes', 'plant extracts activating caspase', 'cytotoxicity assay', 'docking phytochemicals to caspase', 'technological advancement for anticancer therapy', 'clinical studies of plant extracts and phytochemicals' and 'herbal drugs approved by FDA' was included. Results: The compilation revealed significance of multiple experimental strategies, traditional research laboratory practices and advanced in silico molecular docking techniques in anticancer therapy. Technological advancement such as MALDI-TOF assisted phytochemical mediated protein target identification and designing promoter for caspases activation and synthesizing functionalized nano carriers for clinical studies has been included for identification of hit molecule and lead optimization. Eugenol and berberine were identified as phytochemicals with potential drug characteristics by both in silico and in vivo studies. Conclusion:The phytochemicals from important Kani tribal medicinal plants via in silico docking and in vivo studies identified could be explored at clinical trials.

Ficus religiosa (Linn.) bark extract secondary metabolites bestow antioxidant property inducing cell cytotoxicity to human breast cancer cells, MDA-MB-231 by apoptosis involving apoptosis-related proteins, Bax, Bcl-2 and PARP

“…Chromatin condensation con rms MDA-MB-231 cell cytotoxicity by extract to be an apoptotic event. Chromatin condensation and DNA fragmentation by caspase-activated endonucleases are characteristics of apoptosis [34,35]. These events are observed during late apoptosis following activation of caspases and degradation of nuclear DNA into nucleosomal units [36,37].…”

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“…The positive control, camptothecin, assayed for cytotoxicity under similar conditions, exhibited EC 50 of 1.28 ± 3.11 mg/mL Table 6. [21][22] . These events are observed during late apoptosis following caspases' activation and nuclear DNA degradation into nucleosomal units [23][24] .…”