Page 376 - IJB-9-6

International Journal of Bioprinting Aflatoxin B1-induced cancer stem cells

Figure 4. FACS analysis of CSCs isolated from HepG2 spheroids treated with aflatoxin B1 concentrations of (a) 0, (b) 1, (c) 2.5, and (d) 5 μM;
(e) percentages of CSCs in HepG2 spheroids at four different aflatoxin B1 concentrations by FACS analysis. *P < 0.05, **P < 0.01, ****P < 0.0001.

B1 increased, the CSCs increased to 12.4% of the whole To date, CSCs have been defined by their clinical
population at aflatoxin B1 of 1 μM, and further increased relevance and roles in cancer pathogenesis, rather than
[56]
to 15% at aflatoxin B1 concentration of 2.5 μM. At aflatoxin their biological characteristics . Therefore, there is no
B1 concentration of 5 μM, the number of CSCs increased fixed standard in terms of which surface markers must
to 20.3% of the total population. This result was consistent be expressed in CSCs, leading to differences in how
with the result obtained through confocal imaging of various studies determined whether a cell population
single spheroids. can be classified as CSCs or not. For example, Nguyen
et al. utilized HepG2 cells and employed only the CD133
4. Discussion marker as the indicator for CSC isolation . However,
[57]
sorting CSCs using only one type of marker may not
In 2020, liver cancer is estimated to account for 4.7% of the yield clinically significant result. In 2021, by reviewing
total new cancer cases globally, and it became the third most the expression of CSCs marker in the literature, Dzobo
lethal cancer type, contributing to 8.9% of total deaths . et al. [1,58] revealed that the expression of only one individual
[53]
Moreover, the current therapeutic strategies for liver marker was not considerably correlated with prognosis. In
cancer have become more demanding due to resistance , other words, classifying CSCs based on at least two markers
[54]
and such problems have been mainly attributed to CSCs . should be recommended. In the present study, we selected
[55]
Regarding drug discovery, CSC is also one of the heated CD133 and ALDH1 markers as the indication for sorting
obstacles to new therapies . Many toxins only target liver CSCs because of their significant roles in displaying
[3]
growing cancer cells and cell cycle, but their efficacies were CSC features . While CD133 is involved a number of
[l]
not promising as expected since they are avoided by slowly pathways related to drug resistance [59,60] , ALDH1 is critical
dividing and dormant CSCs . Meanwhile, CSC markers for oxidizing intracellular aldehydes and facilitates cell
[1]
[61]
have been observed to exist on normal stem cells, human proliferation . The relative amount of approximately 6%,
[62]
embryonic stem cells, or human tissues . Antibody–drug reflected by analysis using both confocal imaging and flow
[5]
conjugates (ADC) may be unable to distinguish targeted cytometry, suggests that this selection was appropriate to
cells from healthy ones, leading to adverse effect and the proposed hypothesis of CSCs, which states that they
toxicity. Likewise, therapies targeting signaling pathways are a rare population in tumors.
like Wnt, Notch, or Hedgehog also face similar challenges,
since these cascades also progress in normal stem cells . Aflatoxin B1 has been widely recognized as a
[2]
Moreover, approaches involving epigenetic processes and carcinogen. Aflatoxin B1’s metabolite, exo-aflatoxin B1-8,9-
quiescent CSCs are limited due to a lack of knowledge epoxide, can lead to various mutations in the p53 protein,
about their function in CSC biology. among which the mutation at the third base codon 249 is
Volume 9 Issue 6 (2023) 368 https://doi.org/10.36922/ijb.0985