Curcumin-Injected Musca domestica Larval Hemolymph: Cecropin Upregulation and Potential Anticancer Effect

Abstract

Over recent decades, much attention has been given to imply the natural products in cancer therapy alone or in combination with other established procedures. Insects have a rich history in traditional medicine across the globe, which holds promise for the future of natural product drug discovery. Cecropins, peptides produced by insects, are components of a defense system against infections and are well known to exert antimicrobial and antitumor capabilities. The present study aimed to investigate, for the first time, the role of curcumin in enhancing the anticancer effect of Musca domestica larval hemolymph. Third larval instars of M. domestica were injected with curcumin and the hemolymph was picked at 4, 8, and 24 h post-curcumin injection. M. domestica cecropin A (MdCecA) was evaluated in control and injected larval hemolymphs. The cytotoxicity on breast cancer cell lines (MCF-7) and normal Vero cells was assessed to be comparable to control larval hemolymph. Curcumin-injected larval hemolymphs exhibited significant cytotoxicity with respect to the uninjected ones against MCF-7; however, Vero cells showed no cytotoxicity. The IC50 was 106 ± 2.9 and 388 ± 9.2 μg/mL for the hemolymphs of injected larvae at 4 and 8 h, respectively, while the control larval hemolymph revealed the IC50 of >500 μg/mL. For mechanistic anticancer evaluation, concentrations of 30, 60, and 100 μg/mL of curcumin-injected larval hemolymphs were examined. A significant G2/M cell cycle arrest was observed, confirming the anti-proliferative properties of hemolymphs over the tested concentrations. The MdCecA transcripts were significantly (p < 0.05) upregulated at 4 and 8 h post-injection, while a significant downregulation was observed after 24 h. Cecropin quantification by LC–MS revealed that MdCecA peptides have the highest expression in the hemolymph of the treated larvae at 8 h relative to the control group. The upregulation of cecropin expression at mRNA and protein levels may be attributed to the curcumin stimulation and linked to the increased cytotoxicity toward the cancer cell line. In conclusion, the results suggest that the apoptotic and anti-proliferative effects of M. domestica hemolymph on MCF-7 cells following the curcumin injection can be used as a natural candidate in future pharmaceutical industries.

Revisiting edible insects as sources of therapeutics and drug delivery systems for cancer therapy

“…Cecropin in combination with other anti-cancer agents like curcumin also resulted in enhanced anticancer effects. Cecropin A levels were elevated in curcumin treated Musca domestica hemolymph and also showed higher cytotoxicity, anti-proliferative activity and induced G2/M cell cycle arrest in MCF-7 cells, but was not cytotoxic to normal vero cells (Mahmoud et al, 2022). The M1-8 peptide (G-W-L-K-K-I-G-K) derived from the N-terminal region of cecropin isolated from the hemolymph of M. domestica larvae induced lysosomal leakage and lysosome mediated apoptosis in human hepatocellular carcinoma cell line, HepG2, and HepG2 xenograft mouse model (Zeng et al, 2023).…”

“…As these bioactive compounds show higher synergistic anticancer efficacy in conjugation with other nature derived bioactive compounds or in combination with chemotherapeutic agents, more research should focus on combination therapy. For example, cecropin shows higher anticancer effects in combination with curcumin (Mahmoud et al, 2022); and, a hybrid vaccine developed by conjugating mellitin with RADA32 (cell assembling peptide), CpG (immune adjuvant) and tumor lysate shows strong antitumor immunological activity in melanoma B16-F10 xenograft mice (Yang K. et al, 2023). There should also be more focus on the mode of delivery of chemotherapeutic agents and/or natural products to the target tumors or cancer sites in order to reduce systemic toxicity and improve therapeutic efficacy.…”

Isolation of Peptide Inhibiting SGC-7901 Cell Proliferation from Aspongopus chinensis Dallas

“…It induced caspase-dependent apoptosis in melanoma cells through the intrinsic mitochondrial pathway, protecting mice against tumor development. In addition, chemicals originating from Bombyx mori , Chrysomya megacephala , Musca domestica , and Holotrichia diomphalia larvae also have certain inhibitory effects on various tumor cells [ 13 , 14 , 15 , 16 ].…”