Molecular mechanisms underlying antitumor activity of camel whey protein against multiple myeloma cells

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• Drug-resistant cancers, including multiple myeloma (MM), pose significant clinical challenges, necessitating the development of novel therapeutic agents.
• Despite advancements, multiple myeloma remains an incurable plasma cell malignancy, highlighting the urgent need for effective treatments.

Purpose of the Study:

• To investigate the therapeutic potential of camel whey protein (CWP) against multiple myeloma (MM) cell lines.
• To determine the impact of CWP on MM cell viability, chemotaxis, apoptosis, and underlying molecular mechanisms.

Main Methods:

• MTT assay to determine CWP's half-maximal inhibitory concentration (IC50) and assess cell viability.
• Flow cytometry to analyze chemotaxis responses to CXCL12 and CWP's pro-apoptotic effects.
• Western blot analysis to elucidate molecular mechanisms, including signaling pathways and apoptosis-related protein expression.

Main Results:

• CWP demonstrated a significant impact on MM cell viability with an IC50 of 50 μg/ml, while sparing normal peripheral blood mononuclear cells (PBMCs).
• CWP significantly inhibited MM cell chemotaxis mediated by CXCL12 and reduced the activation of key signaling pathways (AKT, mTOR, PLCβ3, NFκB, ERK) via the CXCL12/CXCR4 axis.
• CWP induced apoptosis by upregulating cytochrome C and increasing pro-apoptotic proteins (Bak, Bax, Bim) while decreasing anti-apoptotic proteins (Bcl-2, Bcl-XL, Mcl-1), leading to cell growth arrest.

Conclusions:

• Camel whey protein exhibits significant anti-multiple myeloma activity.
• CWP demonstrates therapeutic potential by inhibiting MM cell proliferation, migration, and inducing apoptosis through modulation of critical molecular pathways.