Modulation of Bax and Bcl-2 genes by secondary metabolites produced byPenicillium rubensJGIPR9 causes the apoptosis of cancer cell lines

Abstract

Search for an efficient anti-cancer compound of natural origin with well-defined mechanisms of action is an important scientific pursuit today, due to cancer being the second leading cause for the death of affected people. The members of the genus Penicillium are one of the important sources of bioactive compounds. In the present study, Penicillium rubens, isolated from a garden soil in Madurai district of Tamil Nadu, was found to produce a highly promising anti-cancer metabolite. The percentage viabilities of HepG2, HeLa and MCF-7 cancer cells treated with the bioactive fraction (P5) isolated from P. rubens, ranged between 40-50% after 96 h. Apoptosis induction was found to be the major reason for the observed reduction in cancer cell proliferation and cell count which was confirmed by caspase activity, DNA fragmentation, clonogenic assay, cell cycle analysis and LDH assays. The upregulation of proapoptotic Bax, coupled with the downregulation of anti-apoptotic Bcl-2 expressions were confirmed by RT-qPCR and flow cytometry methods. The current study also indicated an upregulation of p53 which further strengthened the apoptogenic property of P5 fraction. Non-toxicity of P5 was demonstrated on normal peripheral lymphocytes. The analysis of P5 fraction through GC-MS indicated the presence of indole-2, 3-(4,4-dimethyl-3-thiosemicarbazone) as one of the major compounds. ARTICLE HISTORY

Efficacy of Penicillium limosum Strain AK-7 Derived Bioactive Metabolites on Antimicrobial, Antioxidant, and Anticancer Activity against Human Ovarian Teratocarcinoma (PA-1) Cell Line

“…In the present context, AK-7 extract significantly induced and influenced the apoptosis mechanism in the PA-1 cell line through a series of mechanisms that finally led to mitochondrial dysfunction and cell death compared to the untreated cell line. Venkatachalam et al (2019) observed increased apoptosis in HepG2, HeLa, and MCF-7 cancer cell lines treated with Penicillium rubens extract; they also observed upregulation of Bcl-2, Bax, and p53 expressions levels significantly increased the apoptotic efficacy [61]. It was evident from the literature that induced cancer cell death is the result of potential metabolites present in the extracts.…”

Gut microbiota-based pharmacokinetic-pharmacodynamic study and molecular mechanism of specnuezhenide in the treatment of colorectal cancer targeting carboxylesterase

“…It has been reported that Candida contains a variety of human commensal species, such as Candida albicans , which can alleviate the intestinal mucosal damage caused by dextran sulfate-induced colitis in mice, exhibit immunomodulatory properties, and maintain intestinal homeostasis [ 50 ]. Penicillium has been reported to produce multiple secondary metabolites that inhibit tumor cell growth [ 51 ]. Aspergillus produces aflatoxins, which can cause opportunistic infections and liver damage in humans [ 52 ], and recent studies have shown that its abundance is increased in the gut of patients with multiple sclerosis [ 53 ].…”

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“…The fungal isolate with promising anti-cancer properties was identified as Penicillium rubens by 18s rRNA sequencing (Biokart India Pvt. Ltd., Bengaluru) 10 . The sequence was submitted to Genbank and the accession number obtained was MH816935 (Penicillium rubens JGIPR9).…”

“…A list of different nutrients used in the single factor system along with the basal media for biomass production (response 1) and concentration of bioactive metabolite (response 2) are listed in Table 1. Culture conditions such as incubation period (day 9-14), pH (3)(4)(5)(6)(7)(8)(9)(10)(11) and temperature (4 °C, RT [24-28 °C], 40 °C and 60 °C) were also considered for enhancing biomass production and quantity of bioactive metabolite. The extraction of metabolite and determination of biomass weight were performed as previously mentioned.…”