Mahmoud Shaymaa, Hassab El-Nabi Sobhy, Hawash Asmaa, El-Seedi Hesham R, Khalifa Shaden A M, Ullah Sami, Al-Sehemi Abdullah G, El-Garawani Islam M
Department of Zoology, Faculty of Science, Menoufia University, Menoufia 32511, Egypt.
Department of Bioscience, Faculty of Dentistry, Sinai University, Ismailia 41632, Egypt.
Molecules. 2022 Feb 27;27(5):1570. doi: 10.3390/molecules27051570.
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.
在最近几十年里，人们非常关注将天然产物单独或与其他既定方法联合用于癌症治疗。昆虫在全球传统医学中有着悠久的历史，这为天然产物药物发现的未来带来了希望。天蚕素是昆虫产生的肽，是抗感染防御系统的组成部分，以具有抗菌和抗肿瘤能力而闻名。本研究旨在首次探究姜黄素在增强家蝇幼虫血淋巴抗癌作用中的作用。给家蝇的三龄幼虫注射姜黄素，并在注射姜黄素后的4小时、8小时和24小时采集血淋巴。在家蝇对照幼虫血淋巴和注射幼虫血淋巴中评估家蝇天蚕素A（MdCecA）。评估其对乳腺癌细胞系（MCF-7）和正常Vero细胞的细胞毒性，结果显示与对照幼虫血淋巴相当。注射姜黄素的幼虫血淋巴对未注射的幼虫血淋巴而言，对MCF-7表现出显著的细胞毒性；然而，Vero细胞未显示出细胞毒性。注射幼虫4小时和8小时血淋巴的IC50分别为106±2.9和388±9.2μg/mL，而对照幼虫血淋巴的IC50>500μg/mL。为了进行抗癌机制评估，检测了浓度为30、60和100μg/mL的注射姜黄素幼虫血淋巴。观察到显著的G2/M期细胞周期阻滞，证实了在所测试浓度下血淋巴的抗增殖特性。注射后4小时和8小时，MdCecA转录本显著上调（p<0.05），而24小时后观察到显著下调。通过液相色谱-质谱法定量天蚕素发现，相对于对照组，MdCecA肽在处理后8小时幼虫的血淋巴中表达最高。天蚕素在mRNA和蛋白质水平的上调可能归因于姜黄素的刺激，并与对癌细胞系细胞毒性的增加有关。总之，结果表明，注射姜黄素后家蝇血淋巴对MCF-7细胞的凋亡和抗增殖作用可在未来制药行业用作天然候选物。
