Introduction:

In recent years, the potential of natural compounds in cancer treatment has gained significant attention. Among them, bromelain, derived from pineapple, has emerged as a promising anticancer agent. This article explores the intriguing phenomenon of autophagy in mammary carcinoma cells and its relationship with apoptosis under the influence of bromelain treatment.

Autophagy and Apoptosis: A Complex Interplay:

Autophagy, a cellular process involved in the degradation and recycling of cellular components, has been linked to various physiological and pathological conditions, including cancer. In this study, we focused on bromelain-induced autophagy in estrogen receptor-positive and negative mammary carcinoma cells. Through the use of monodansylcadaverine localization, we observed a distinct autophagic response in MCF-7 cells treated with bromelain. Interestingly, this autophagic phenomenon was followed by apoptotic cell death, characterized by sub-G1 cell fraction, chromatin condensation, and nuclear cleavage.

The Role of Autophagy in Facilitating Apoptosis:

To gain further insights into the relationship between autophagy and apoptosis, we employed 3-Methyladenine (MA), an autophagy inhibitor. Pretreatment with MA resulted in a reduction of bromelain-induced autophagy levels and a subsequent decline in apoptotic population, suggesting that autophagy plays a facilitating role in apoptosis. Moreover, the addition of a caspase-9 inhibitor, Z-LEHD-FMK, augmented autophagy levels, inhibited morphological apoptosis, but did not prevent cell death, indicating the complex interplay between these two cellular processes.

MAP Kinases: Key Players in Bromelain-Induced Autophagy:

Further investigation into the molecular mechanisms underlying bromelain-induced autophagy revealed the influence of mitogen-activated protein kinases (MAPKs). We observed the downregulation of extracellular signal-regulated kinase ½ (ERK½) phosphorylation, while c-jun N-terminal kinase (JNK) and p38 kinase were upregulated. Interestingly, MA had no impact on bromelain-suppressed ERK½ activation but downregulated JNK and p38 activation. Additionally, the use of MAPK inhibitors enhanced autophagic ratios, suggesting the involvement of MAP kinases in bromelain-induced autophagy. Notably, all three MAPKs remained constantly activated throughout the study.

Autophagy-Related Protein Expression:

To further elucidate the mechanisms underlying bromelain-induced autophagy, we examined the expression of autophagy-related proteins. Bromelain treatment led to the upregulation of light chain 3 protein B II (LC3BII) and beclin-1, both known markers of autophagy. Interestingly, inhibition of ERK½ increased the expressions of LC3BII and beclin-1, while inhibition of p38 and JNK decreased their expression levels. These findings indicate that bromelain-induced autophagy is positively regulated by p38 and JNK but negatively regulated by ERK½.

Exploiting Bromelain’s Autophagy-Inducing Potential in Breast Cancer Therapy:

The autophagy-inducing property of bromelain holds great promise in the field of breast cancer therapy. By understanding the intricate interplay between autophagy and apoptosis, we can potentially develop novel therapeutic strategies that harness the full potential of bromelain in combating breast cancer.

Conclusion:

In conclusion, this study highlights the remarkable ability of pineapple bromelain to induce autophagy, subsequently facilitating apoptotic responses in mammary carcinoma cells. The findings shed light on the complex relationship between autophagy and apoptosis, as well as the involvement of MAP kinases in bromelain-induced autophagy. Further research and exploration of bromelain’s potential in breast cancer therapy are warranted, offering new avenues for innovative treatment approaches.

References:

Bhui, K., Tyagi, S., Prakash, B., & Shukla, Y. (Year). Pineapple bromelain induces autophagy, facilitating apoptotic response in mammary carcinoma cells. PubMed